Arylamide derivatives as allosteric inhibitors of the integrin α2β1/type I collagen interaction
| Autor: | Meredith W. Miller, Dahui Liu, Joel S. Bennett, William F. DeGrado, Hang Yin, Gaston Vilaire, David T. Moore, Lars Ole Gerlach |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Clinical Biochemistry Allosteric regulation Integrin Pharmaceutical Science Enzyme-Linked Immunosorbent Assay Biochemistry Collagen Type I Collagen receptor Protein–protein interaction Structure-Activity Relationship Allosteric Regulation Drug Discovery Humans Platelet Molecular Biology Binding Sites Molecular Structure biology Cell adhesion molecule Chemistry Organic Chemistry Stereoisomerism Amides In vitro biology.protein Molecular Medicine Integrin alpha2beta1 Hydrophobic and Hydrophilic Interactions Type I collagen Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 16:3380-3382 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2006.04.037 |
| Popis: | We herein report a group of allosteric inhibitors of integrin alpha(2)beta(1) based on an arylamide scaffold. Compound 4 showed an IC(50) of 4.80 microM in disrupting integrin I-domain/collagen binding in an ELISA. These arylamide compounds are able to block collagen binding to integrin alpha(2)beta(1) on the platelet surface. Further we find that compound 4 recognizes a hydrophobic cleft on the side of the alpha(2) I-domain, suggesting an alternative targeting site for drug development. |
| Databáze: | OpenAIRE |
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